The enzyme 3-hydroxy-3-methyl glutaryl Coenzyme A reductase catalyzes the rate limiting reaction in hepatic cholesterol biosynthesis under most physiological conditions. This project is proposed to determine the steady-state kinetic mechanism of the enzyme catalyzed reaction and thus to evaluate the effects of estimated cellular levels of substrates and products in normal and diabetic rats on the rate of cholesterol biosynthesis. In addition it is proposed to elucidate the effects of various likely metabolic intermediates on the HMG-CoA reductase catalyzed reaction as these intermediates are varied in concentration throughout the ranges estimated to exist under physiological conditions of variations in diet and in the presence of diabetes. Finally, it is proposed to determine the kinetic effects of the lipid composition of the microsomal membrane and of the lipid component of the enzyme-lipid complex on the HMG-CoA reductase catalyzed reaction.